Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells

被引：45

作者：

Reitman, Zachary J. ^{[1
,2
,3
]}

Paolella, Brenton R. ^{[1
,2
]}

Bergthold, Guillaume ^{[4
,5
]}

Pelton, Kristine ^{[6
]}

Becker, Sarah ^{[6
]}

Jones, Robert ^{[6
]}

Sinai, Claire E. ^{[7
]}

Malkin, Hayley ^{[1
]}

Huang, Ying ^{[6
]}

Grimmet, Leslie ^{[8
]}

Herbert, Zachary T. ^{[8
]}

Sun, Yu ^{[1
]}

Weatherbee, Jessica L. ^{[1
]}

Alberta, John A. ^{[1
]}

Daley, John F. ^{[9
]}

Rozenblatt-Rosen, Orit ^{[2
]}

Condurat, Alexandra L. ^{[2
,7
,10
]}

Qian, Kenin ^{[7
]}

Khadka, Prasidda ^{[1
]}

Segal, Rosalind A. ^{[1
]}

Haas-Kogan, Daphne ^{[11
]}

Filbin, Mariella G. ^{[2
,7
,10
]}

Suva, Mario L. ^{[2
,12
,13
,14
,15
]}

Regev, Aviv ^{[2
,15
,16
]}

Stiles, Charles D. ^{[1
]}

Kieran, Mark W. ^{[7
,10
,17
,22
]}

Goumnerova, Liliana ^{[18
]}

Ligon, Keith L. ^{[2
,6
]}

Shalek, Alex K. ^{[2
,19
,20
,21
]}

Bandopadhayay, Pratiti ^{[2
,7
,10
]}

Beroukhim, Rameen ^{[1
,2
,9
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02215 USA

[4] Hoffmann La Roche AG, Prod Dev, Innovat Pediat Oncol Drug Discovery, CH-4070 Basel, Switzerland

[5] Ctr Hosp Univ Strasbourg, Serv Hematol Oncol Pediat, F-67000 Strasbourg, France

[6] Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02215 USA

[7] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA 02215 USA

[8] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02215 USA

[9] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[10] Harvard Med Sch, Dept Pediat, Boston, MA 02215 USA

[11] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA

[12] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[13] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[14] Harvard Med Sch, Boston, MA 02114 USA

[15] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA

[16] MIT, Howard Hughes Med Inst, Dept Biol, Koch Inst, Cambridge, MA 02139 USA

[17] Bristol Myers Squibb, Devens, MA 01434 USA

[18] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02215 USA

[19] MIT, Dept Chem, Inst Med Engn & Sci, Cambridge, MA 02139 USA

[20] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[21] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA

[22] Bristol Myers Squibb, Lawrenceville, NJ 08648 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

LOW-GRADE GLIOMAS; DEATH-LIGAND; RNA-SEQ; GENOMIC ANALYSIS; EXPRESSION; METHYLATION; SENESCENCE; DIVERSITY; LOCATION; CHILDREN;

D O I：

10.1038/s41467-019-11493-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.

引用

页数：17

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